New gene findings: what are the implications for OA? (1990). Syntex Laboratories, Inc. 17(10):1,9.

Adey WR (1993). Whispering between cells: electromagnetic fields and regulatory mechanisms in tissue. Frontier Prospectives, 3 (2):21-25.
Summary: "At the core of observed sensitivities to low-level EM fields are a series of cooperative processes. One such series involves calcium ion building and release. Available evidence points to their occurrence at cell membranes and on cell surfaces in the essential first steps of detecting EM fields. Also, attention is now directed to newly defined roles for free radicals, that may also participate in highly cooperative detection of weak magnetic fields, 'even at levels below thermal (kT) noise."(p.21) "It is at the atomic level that physical processes, rather than chemical reactions in the fabric of molecules, appear to shape the transfer of energy and the flow of signals in living systems." (p. 24)

Adey WR (1988). Physiological signaling across cell membranes and cooperative influences of extremely low frequency electromagnetic fields. In: Frohlich H, ed. Biological Coherence and Response to External Stimuli. Springer-Verlag, 148-170.
Summary: Discussion of required field intensities as they affect degrees of cooperativity.

Akizuki S, Mow VC, Muller F, Pita JC, Howell DS, Manicourt DH (1986). Tensile properties of human knee cartilage: I. Influence of ionic conditions, weight bearing, and fibrillation on the tensile modulus. J Orthop Res, 4(4):397-392.
Summary: "The flow-independent (intrinsic) tensile modulus of the extracellular matrix [ECM] of human knee joint cartilage has been measured for normal, fibrillated, and osteoarthritic (removed from knee joint replacements) cartilage. ...The tensile modulus of the ECM correlates strongly with the collagen/proteoglycan ratio." (p.379)

Anderson JC, Eriksson C (1968). Electrical properties of wet collagen. Nature, 218:166-168.
Summary: "The electrical properties of dried collagen and bone have been studied by Fukada and Yasuda. Both were shown to be piezoelectric, producing a measurable potential between opposite faces when stressed and also deforming on application of a voltage.... The mechanism of streaming potential at its simplest depends on the absorption of one type of ion on the surface of the molecule, with an associated diffuse layer of ions of the opposite type extending out from the molecular surface. When the liquid streams past the molecule there is a net transport of one type of ion with a resulting potential gradient, which may be measured by means of electrodes placed in the stream. The magnitude of the streaming potential is dependent on the type of molecule and the pH of the solution." (p.166) "These results with wet collagen imply that, because it exhibits no piezoelectric effect, it belongs to a group of higher symmetry than does the dry material." (p.167)

Bassett CAL, Pawluk RJ (1972). Electrical behavior of cartilage during loading. Science, 178:982-983.
Summary: "When cartilage is deformed, it becomes electrically polarized. At least two mechanisms seem to underlie this phenomenon, namely, a short-duration, high-amplitude, piezoelectric-like response and a longer-duration, lower-amplitude response secondary to streaming potentials. the polarity of articular cartilage during loading could hypothetically facilitate joint lubrication."(p.982) "... regions of growth are characteristically electro-negative.... Joint lubrication during loading occurs largely as a result of the adherence of sodium hyaluronate to the articular surface. This biopolymer is a strong polyanion and would be expected to adhere more effectively to a positively charged surface than to one which was negatively charged. Since cartilage itself is fabricated to a large degree of protein-polysaccharides, which are negatively charged, it would seem appropriate to assume that Nature developed an electrostatically based method to facilitate cartilage lubrication at the moment of loading."(p.983)

Benveniste J (1993). Transfer of biological activity by electromagnetic fields. Frontier Prospectives, 3(2):13-15.
Summary: "The essential molecular functions appear in fact to be determined by electromagnetic mechanisms. A possible role of molecular structures would be the carrying of electric charges which generate, in the aqueous environment, a field specific to each molecule. Those exhibiting such coresonating or opposed fields ("electroconformational coupling") could thus communicate, even at a distance. Therefore a minute variation in the structure of molecules (plus or minus an atom, or a rearrangement of an amino acid, for example), which even slightly modifies their radiating field, would allow their message to be received or not by a receptor, as in the FM waveband." (p.15)

Bjelle A (1977). Glycosaminoglycans in human articular cartilage of the lower femoral epiphysis in osteoarthritis. Scand J Rheumatology, 6:37-44.

Blakeslee S (1992, May 12). Magnetic crystals, guides for animals, found in humans. New York Times, C1,C12.

Brandt KD, Radin E (1987). The physiology of articular stress: Osteoarthritis. Hosp Pract, 103-126.
Summary: Describes some of the mechanisms of OA.

Breger L, Blumenthal NC (1993). Electromagnetic field enhancement of membrane ion transport. Proceedings of the Thirteenth Annual Meeting of the Bioelectrical Repair and Growth Society; October 10-13, 1993; Dana Point, CA. BRAGS, 38.
Summary: Experiments to test Liboff's hypothesis concerning magnetic fields and calcium diffusion were performed using artificial and biological membranes with no results.

Buckwalter JA, Mow VC (1992). Cartilage repair in osteoarthritis. In: Moskowitz RW, Howell DS, Goldberg VM, Mankin HJ, eds. Osteoarthritis: Diagnosis and Medical/ Surgical Management. 2nd ed. Philadelphia: W. B. Saunders Company, chap 4.

Calvino B, Villanueva L, Le Bars D (1987). Dorsal horn (convergent) neurones in the intact anaesthetized arthritic rat. I. Segmental excitatory influences. Pain, 28:81-98.
Summary: "In healthy rats, the convergent and non-noxious neurones of laminae 3-6 are generally almost silent in the absence of an any stimuli within the receptive field. This was also true in the present study for the "typical" neurons; however about half (58%) of the "atypical" neurons exhibited a high level, background discharge which sometimes showed dramatic increases...."(p.93)

Calvino B, Villanueva L, Le Bars D (1987). Dorsal horn (convergent) neurones in the intact anaesthetized arthritic rat. II. Heterotopic inhibitory influences. Pain, 31:359-379.
Summary: "It is concluded that the input for triggering heterotopic inhibitory influences by mechanical stimuli is altered in the arthritic rat, a model of chronic pain. This is consistent with the known lowering in threshold of nociceptive afferents innervating the joint capsule, induced by arthritis."(p.360)

Caterson B, Lowther DA (1978). Changes in the metabolism of the proteoglycans from sheep articular cartilage in response to mechanical stress. Biochim Biophys Acta, 540:412-422.
Summary: "Cartilage integrity can be controlled by many factors which influence the balance between synthesis and breakdown of its components. The results presented here suggest that articular cartilage has the capacity to respond to the mechanical stresses to which it is exposed and that mechanical stress and motion are required for the maintenance of the cartilage constituents at normal physiological levels." (p. 421)

Cochran GVB, Otter MW, Bieber W, Wu D (1993). Streaming potentials associated with gap healing in canine tibia. Proceedings of the Thirteenth Annual Meeting of the Bioelectrical Repair and Growth Society; October 10-13, 1993; Dana Point, CA. BRAGS, 9.
Summary: "This experiment measures the first in vivo measurements of SPs from bone callus; it identified two factors which affect the electrical output. First, the magnitude of SPs correlated roughly with the magnitude of total strain on the callus; this was the dominant effect. As healing progressed, and the enchondral layer became thinner and eventually disappeared, the signals decreased as strain tended to be reduced and to become equalized between callus and adjacent bone. Second, the signal strength...tended to increase as the new bone became more dense, thus supporting the prior observation that new and remodeling bone generates lower amplitude SPs/strain (1) than does normal cortical bone..." (p 9)

Davey CL, Kell DB (1990). The dielectric properties of cells and tissues: What can they tell us about the mechanisms of field/cell interactions? In: O'Connor ME, Bentall RHC, Monahan JC, eds. Emerging Electromagnetic Medicine. New York, NY:Springer-Verlag, 19-43.
Summary: In cell suspension, as the frequency is increased, permitivity falls and conductivity rises. [Implication: at low Hz, permitivity highest, but conductance low.] At low frequencies, cell membrane behaves as non-conductors suspended in a conducting medium; most of the current is flowing in the suspension around the cells. As it takes time for ion movements to occur, low frequencies allow time for it to occur. Oscillations caused by rapid alternating frequencies can generate heat; low frequencies are isothermal. "If fields can affect enzymes and cells, [one should expect] to be able to tailor a waveform as a therapeutic agent in much the same way as one now modulates chemical structures to obtain pharmacological selectivity and perhaps withhold many of the side-effects common to pharmaceutical substances." [ref 58-Kell in a Wales local journal.]

DeWitt MT, Handley CJ, Oakes BW, Lowther DA (1984). In vitro response of chondrocytes to mechanical loading, the effect of short term mechanical tension. Conn Tissue Res, 12:97-109.
Summary: "The results presented in this paper demonstrate that it was possible to elicit a direct response in vitro by chondrocytes to mechanical stimuli over a 24 h period. There was an increase in the rate of proteoglycan synthesis by the chondrocyte cultures..." (p107) "However, high impact loads or abnormal loading of synovial joints results in loss of proteoglycan from articular cartilage, fibrillation of this tissue and cell death reflected in a loss of cellularity, changes which resemble those seen in osteoarthritis." (p109)

Dunham J, Shackleton DR, Nahir AM, Billingham MEJ, Bitensky L, Chayen J, et al. (1985). Altered orientation of glycosaminoglycans and cellular changes in the tibial cartilage in the first two weeks of experimental canine osteoarthritis. J Orthop Res, 3:258-268.
Summary: "Changes in the cellularity and in the nature of the matrix were studied in the cartilage of the tibial plateau in experimentally induced arthritis in the dog,.... The orientation of the glycosaminoglycans was assessed by the new 'induced birefringence' method. The results indicated that only the region of the medial tibial cartilage that was unprotected by the meniscus was affected, showing increased water content, loss of superficial cells, and a crease in orientation of the glycosaminoglycans. Whereas the birefringence [orientation] of the collagen was unaffected, the superficial area that lacked oriented glycosaminoglycans was markedly increased; this may be a useful indicator of early osteoarthritic changes."(p. 258)

Eyre DR (1991). Cartilage expression of a type II collagen mutation in an inherited form of osteoarthritis associated with a mild chondrodysplasia. J Clin Invest, 87:357-361.
Summary: "We postulate that the presence of the mutant protein molecules in the extracellular collagen reduces the durability of the articular cartilage and manifests as the disorder, severe primary OA. The fibrils may be less able in the long term to cope with the mechanical stresses that articular cartilage endures, perhaps through defects in material properties. In addition the collagen may be more susceptible to extracellular proteases that are active in matrix remodeling but which do not normally degrade the collagen triple-helix. ...Because failure of the underlying collagen fabric of cartilage appears to be a key, irreversible event in the process of joint destruction in OA in all its subsets, defining how this single amino acid substitution is etiologically associated with severe but otherwise typical disease manifestations may prove instructive in understanding osteoarthritic joint failure."(p.360)

Ficat C, Maroudas A (1975). Cartilage of the patella. Topographical variation of glycosaminoglycan content in normal and fibrillated tissue. Ann Rheum Dis, 34:515-519.
Summary: "The glycosaminoglycan content of normal cartilage is lower in the knee than in the hip. This fact, together with the existence of high pressures during load bearing, may be responsible for the greater frequency of destructive lesions affecting the cartilage of the patella compared with that of the hip."

Liu H, Abbott J, Bee JA. Pulsed electromagnetic fields influence hyaline cartilage extracellular matrix composition without affecting molecular structure. Osteoarthritis Cartilage. 1996 Mar; 4 (1): 63-76.
Summary: This study focuses upon the effect of PEMF on the composition and molecular structure of cartilage proteoglycans. Sixteen-day-old embryonic chick sterna were explanted to culture and exposed to PEMF for a 3h/day for 48 h. PEMF treatment did not affect the DNA content of explants but stimulated elevation of glycosaminoglycan content in the explant and conserved the tissue's histological integrity. These results demonstrate that exposure of embryonic chick cartilage explants to PEMF for 3h/day maintains a balanced proteoglycan composition by down-regulating its turnover without affecting either molecular structure or function.